Pharmaceutical agents with rapid antidepressant effects are a new and promising paradigm in the research for treatment of MDD. A potential therapeutic target is glutamate based signal transmission because glutamate transmission is abnormally regulated in the limbic/cortical areas of many depressed people. Glutamatergic modulating agents, in particular ketamine, have been shown to induce rapid antidepressant effects both in both preclinical models and humans. Additionally, ketamine has been shown to have persistent antidepressive effect.